缺氧(环境)
血管生成
上皮-间质转换
癌症研究
热休克蛋白
细胞迁移
医学
细胞生长
细胞
血管内皮生长因子
MTT法
食管癌
细胞培养
转移
生物
癌症
化学
内科学
生物化学
血管内皮生长因子受体
氧气
有机化学
基因
遗传学
作者
Ching Tzao,Chin‐Kun Wang
出处
期刊:Diseases of The Esophagus
[Oxford University Press]
日期:2021-09-01
卷期号:34 (Supplement_1)
标识
DOI:10.1093/dote/doab052.547
摘要
Abstract Hypoxia is known as an important trigger for the development of metastases in human cancers. Heat shock proteins (Hsps) are up-regulated by cellular stressors including hypoxia. To date, the functional role of Hsps within the hypoxic tumor microenvironment for esophageal squamous cell cancer (ESCC) remains poorly defined. Methods CoCl₂ was used to induce hypoxia in cultured ESCC cells which was confirmed by 2′,7′ –dichlorofluorescin diacetate (DCFDA) assay. 7-Dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), a selective Hsp90 inhibitor, was used to treat 2 ESCC cell lines, KYSE-170 and -510 cells pretreated with or without CoCl₂₂₂₂₂ in different concentrations, followed by cytotoxicity (MTT) and migration assays. In parallel, expression of Hsp90, vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1α (HIF-1α), and markers related to epithelial-mesenchymal transition (EMT) such as snail/E-cadherin, by immunoblot or ELISA while analyzing cell proliferation and migration of treated ESCC cells. Results CoCl₂ induced hypoxia was supported by induction of reactive oxygen species (ROS). CoCl₂ (200 μM) significantly suppressed cell viability and proliferation with a concomitant up-regulation of VEGF and HIF-1α in a dose-dependent fashion. In contrast, cell migration was significantly increased in response to CoCl₂ while down-regulating E-cadherin with a concomitant increase in Snail expression. 17-DMAG decreased expression of VEGF and HIF-1α while inhibiting cell migration and invasion. Conclusion Our data demonstrate that CoCl2 induced hypoxia promotes EMT and angiogensis, which are inhibited by 17-DMAG. These results suggest that hypoxia induced EMT and angiogensis is Hsp90 dependent in ESCC.
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